NM_000285.4(PEPD):c.634G>C (p.Ala212Pro) AND Prolidase deficiency

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 20, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000195145.11

Allele description [Variation Report for NM_000285.4(PEPD):c.634G>C (p.Ala212Pro)]

NM_000285.4(PEPD):c.634G>C (p.Ala212Pro)

Gene:

PEPD:peptidase D [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.11

Genomic location:

Preferred name:

NM_000285.4(PEPD):c.634G>C (p.Ala212Pro)

HGVS:

NC_000019.10:g.33463032C>G
NG_013358.2:g.63862G>C
NM_000285.4:c.634G>CMANE SELECT
NM_001166056.2:c.548+15014G>C
NM_001166057.2:c.442G>C
NP_000276.2:p.Ala212Pro
NP_000276.2:p.Ala212Pro
NP_001159529.1:p.Ala148Pro
NC_000019.9:g.33953938C>G
NG_013358.1:g.63862G>C
NM_000285.3:c.634G>C

Protein change:

A148P

Links:

dbSNP: rs747700126

NCBI 1000 Genomes Browser:

rs747700126

Molecular consequence:

NM_001166056.2:c.548+15014G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000285.4:c.634G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001166057.2:c.442G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Prolidase deficiency
Identifiers:: MONDO: MONDO:0008221; MedGen: C0268532; Orphanet: 742; OMIM: 170100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000246184	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV005185225	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (May 20, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000246184

GeneReviews

no classification provided

not provided

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV005185225

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(May 20, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A broad spectrum of developmental delay in a large cohort of prolidase deficiency patients demonstrates marked interfamilial and intrafamilial phenotypic variability.

Falik-Zaccai TC, Khayat M, Luder A, Frenkel P, Magen D, Brik R, Gershoni-Baruch R, Mandel H.

Am J Med Genet B Neuropsychiatr Genet. 2010 Jan 5;153B(1):46-56. doi: 10.1002/ajmg.b.30945.

PubMed [citation]

PMID:: 19308961

Details of each submission

From GeneReviews, SCV000246184.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005185225.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Variant summary: PEPD c.634G>C (p.Ala212Pro) results in a non-conservative amino acid change located in the Peptidase M24 domain (IPR000994) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249576 control chromosomes. c.634G>C has been reported in the literature in multiple individuals affected with Prolidase Deficiency (example: Falik-Zaccai_2010). These data indicate that the variant is very likely to be associated with disease. The following publication has been ascertained in the context of this evaluation (PMID: 19308961). ClinVar contains an entry for this variant (Variation ID: 209997). Based on the evidence outlined above, the variant was classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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